This proposal is concerned with the evaluation of the therapeutic value of fructose-1, 6-diphosphate (FDP) in several different etiological types of lethal shock. The most important indicator of the therapeutic effectiveness of this agent to be considered will be the survival of the animal. The present working hypothesis is that in any etiological type of shock there is a deficit in endogenous energy production via oxidative metabolic pathways arising either from hypoperfusion or impaired oxygen utilization. Under such circumstances aerobic glycolysis tends to compensate for the energy deficit arising from failure of oxidative metabolism by increasing its catabolic rate. However, after this initial increase, glycolysis becomes inhibited by acidosis at the phosphofructokinase (PFK) step. Hypothetically, administration of FDP should provide the substrate that bypasses this metabolic block, and act as a metabolic regulator capable of influencing the activity of PFK and pyruvate kinase in normally perfused and ischemic tissues. This hypothesis has been tested in (1) acute myocardial ischemia in dogs, (2) normothermic ischemic cardiac arrest, (3) hypotensive hemorrhagic shock, (4) normotensive hemorrhagic shock, (5) lethal endotoxin shock, (6) lethal traumatic shock, (7) tourniquet shock, (8) organ preservation and other energy deficient states. In these paired studies, hemodynamic, metabolic and histologic findings in the FDP treated animals were significantly improved (compared to controls) and significant reduction in mortality rates with FDP treatment was achieved. Therefore, it is the goal of this proposal to test the therapeutic effects of FDP in hemorrhagic, endotoxin, tourniquet and burn shock. The experimental animals to be used in these studies will be dogs and pigs. The dogs will be used in hemorrhagic, endotoxin and tourniquet shock, while the pigs will be used in the burn studies because the biologic and metabolic characteristics of pig skin are generally considered to most closely approach that of man. The major end point of this study will be the survival of the animal. Hemodynamic and metabolic data will be compared between the FDP and controls and statistically evaluated. The data obtained up to now with this agent indicate that this intervention could be of clinical importance in the treatment of different etiological types of shock